Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

AUTOR(ES)

Appelmelk, Ben J.

FONTE

American Society for Microbiology

RESUMO

Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS) expresses the human blood group antigens Lewis x (Lex), Ley, and H type I. In this report, we demonstrate that the H type I epitope displays high-frequency phase variation. One variant expressed Lex and Ley and no H type I as determined by serology; this switch was reversible. Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open reading frame homologous to glycosyltransferases) yielded a transformant with a serotype similar to the phase variant. Structural analysis of the NCTC 11637 LPS confirmed the loss of the H type I epitope. Sequencing of JHP563 in strains NCTC 11637, an H type I-negative variant, and an H type I-positive switchback variant showed a C14 (gene on), C13 (gene off), and C14 tract, respectively. Inactivation of strain G27, which expresses Lex, Ley, H type I, and Lea, yielded a transformant that expressed Lex and Ley. We conclude that JHP563 encodes a β3-galactosyltransferase involved in the biosynthesis of H type I and Lea and that phase variation in H type I is due to C-tract changes in this gene. A second H type I-negative variant (variant 3a) expressed Lex and Lea and had lost both H type I and Ley expression. Inactivation of HP093-HP094 resulted in a transformant expressing Lex and lacking Ley and H type I. Structural analysis of a mutant LPS confirmed the serological data. We conclude that the HP093-HP094 α2-fucosyltransferase (α2-FucT) gene product is involved in the biosynthesis of both Ley and Lex. Finally, we inactivated HP0379 in strain 3a. The transformant had lost both Lex and Lea expression, which demonstrates that the HP0379 gene product is both an α3- and an α4-FucT. Our data provide understanding at the molecular level of how H. pylori is able to diversify in the host, a requirement likely essential for successful colonization and transmission.

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